2 Translational lung cancer research, Vol 4, No 1 February 215 Introduction Lung cancer is the leading cause of cancer-associated death in the world (1). Most non-small cell lung cancer (NSCLC) patients are diagnosed at a relatively late stage, and platinum-based first line chemotherapy is prescribed as a part of standard treatment for advanced NSCLC patients. However, the factor that may predict survival and treatment response is limited. 18 F-fluorodeoxyglucose positron emission tomography/ computed tomography ( 18 F-FDG PET/CT) is a wellestablished technique for diagnosis and staging in cancer (2,3). The association between higher maximum standardized uptake value (SUV max ) in 18 F-FDG PET/CT and poor prognosis or treatment response in cancer patients has been reported in several prior studies (4,5). SUV, a semi-quantitative measurement of FDG uptake, in the primary tumor site of NSCLC has been demonstrated to be correlated with proliferation (4,5) and aggressiveness (6,7). In 213, Stiles et al. (8) established the SUV max to tumor size ratio (SUV max /tumor size) in his study. SUV max /tumor size was revealed to be associated with survival in 53 patients who were undergoing resection and histologically diagnosed NSCLC, and was stronger than SUV max alone. However, the association between SUV max or SUV max /tumor size and therapy response or survival in advanced NSCLC patients is still unclear. The aim of this study is to evaluate the predicting and prognostic significance of pretreatment SUV max or SUV max / tumor size in advanced NSCLC patients. Patients and methods Study population The retrospective study protocol was approved by the Hospital Ethics Committee. Patients hospitalized from January 27 to July 211 in Department of Respiratory Medicine were included. Inclusion criteria were: (I) histologically or cytologically diagnosed NSCLC; (II) had a pretreatment 18 F-FDG PET/CT scanning; (III) in stage IIIB and IV, including those in stage IIIA but not able to surgery or not accept the operation; (IV) had no history or concurrent diagnosis of another type of cancer; (V) overall survival (OS) >3 months; (VI) the clinical data should be available. Ratio of SUV max to primary tumor size Scans were performed by a dedicated 16-slice whole-body 19 PET/CT scanner after the patients injected with pyrogenfree 18 F-FDG 1 to 15 mci. SUV max values were obtained by drawing the regions of interest over the most intense slice of the primary tumor by correcting for the injected dose and the patient s weight. The tumor diameter in the primary site was also analyzed. Therapy response and survival analyses Therapeutic response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) by CT scans or 18 F-FDG PET/CT performed after two cycles of chemotherapy. Clinical responses were classified as disease control rate () and progressive disease (). OS was defined as the time in months between the pathological diagnosis and the date of death, progressionfree survival (PFS) as the time between pathological diagnosis and progression disease, and post-progression survival (PPS) as the time between progression disease and the date of death. Patients who were alive were censored at the time of the last clinical follow-up. Statistical analyses Statistical analyses were performed using the SPSS statistical software program (version 18. for windows). The continuous variables SUV max, tumor size, and SUV max / tumor size were dichotomized by a median split. Survival was calculated with the Kaplan-Meier method, and groups were compared with the log-rank test. Multivariate analysis was carried out with the Cox proportional hazards model. A significance level of 5 was used for covariate entry. P values less than 5 were considered to be statistically significant. Results Patient characteristics Total 237 consecutive advanced NSCLC patients were enrolled. However, 49 patients were excluded because they took no therapy, transferred to other hospitals or died within 3 months. In 188 patients who had pretreatment 18 F-FDG PET/CT, six patients with concurrent chemoradiotherapy and one patient with a second primary extrapulmonary cancer were excluded. Final 181 patients were included in the further analysis. The characteristics of the 181 patients were listed in Table 1,

5 22 Chen et al. SUV max /tumor size is a prognostic factor in advanced NSCLC A 15 P=.588 B 4 P=9 SUV max 1 5 SUV max /tumor size C SUV max E SUVmax P=999 P=72 D SUV max /tumor size SUV max /tumor size F P=68 P=565 Figure 1 Relationship of SUV max, SUV max /tumor size and RECIST responses (A and B); relationship of SUV max, SUV max /tumor size and RECIST responses in subgroup of chemotherapy (C and D); relationship of SUV max, SUV max /tumor size and RECIST responses in subgroup of EGFR-TKI therapy (E and F). SUV max, maximum standardized uptake value; RECIST, the Response Evaluation Criteria in Solid Tumors;, disease control rate;, progressive disease. Discussion Our study is the first clinical study to evaluate the prognostic value of SUV max /tumor size in advanced NSCLC patients. SUV max /tumor size is demonstrated to be significantly correlated with survival of patients in this present study. As a promising functional marker, SUV max /tumor size is an available factor for predicting outcome in advanced NSCLC patients. As we known, a tumor did not always have a uniform shape and a homogeneous composition, so tumor diameter could not represent the real tumor burden. Other functional parameters, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were suggested to have prognostic value in previous studies (9,1). MTV and TLG were integrated both tumor volume and biologically relevant metabolic data and was defined as the mean standardized uptake value multiplied by the MTV. However, the volumetric functional assessment could only be made consistently with the advance of image analysis tools and 3-dimensional display techniques. SUV max /tumor size, taken the real tumor burden the tumor diameter together, is much more simple to perform than MTV or TLG and have the efficiency in clinic, making the result more feasible and credible (11,12). Stiles et al. (8) provided the evidence in his study that SUV max /tumor size was a stronger independent predictor of survival than SUV max alone. However, all the patients

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